Niemann-Pick Disease Type C in Adulthood โ€“ A Psychiatric and Neurological Disorder

Mark Walterfang, Dennis Velakoulis
European Psychiatric Review, 2010;3(1):16-20
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Abstract

Niemann-Pick disease type C (NPC) is a rare neurovisceral lipid storage disorder resulting from autosomal recessively inherited loss-of-function mutations in either Npc1 or Npc2. This disrupts intracellular lipid transport, leading to the accumulation of lipid products in the late endosomes and lysosomes. Affecting both children and adults, it exhibits a less rapid disease course in older patients, where it is characterised by slow cognitive decline, neuropsychiatric illness, ataxia and dystonia. As NPC is heterogeneous in presentation, it is often misdiagnosed as other movement or psychiatric disorders, highlighting the need for better awareness of this disease among clinicians. NPC is a progressive disorder and the only currently available disease-specific drug for its treatment is miglustat, which has shown positive outcomes in clinical studies. While other medications have been tested in animal models with encouraging results, they have yet to be trialled in human subjects.

Support: The publication of this article was funded by Actelion. The views and opinions expressed are those of the authors and not necessarily those of Actelion.
Keywords
Niemann-Pick disease type C (NPC), adult-onset, lipid storage disorder, genetic mutation, neuropsychiatric disorder, miglustat, vertical gaze palsy, misdiagnosis, glycosphingolipids, progressive disorder
Disclosure Mark Walterfang has served on local and international advisory boards for Actelion, which is the manufacturer of miglustat (Zavesca). Dennis Velakoulis has no conflicts of interest to declare.
Received: May 25, 2010 Accepted June 14, 2010
Correspondence: Mark Walterfang, Consultant Neuropsychiatrist, Neuropsychiatry Unit, Level 2, John Cade Building, Royal Melbourne Hospital, Corner Grattan St and Royal Parade, Melbourne 3050, Australia. E: mark.walterfang@mh.org.au

Niemann-Pick disease type C (NPC) is a rare and fatal neurovisceral lipid storage disorder that affects both children and adults. Whereas the disease in children is characterised by mental retardation, seizures and often rapid neurodegeneration, in adults the disease is characterised by slow cognitive decline, major neuropsychiatric illness and the development of ataxia and dystonia.1

The data are limited in terms of the epidemiology of NPC. This disease is pan-ethnic, and two genetic isolates have been described in French Arcadians in Nova Scotia and Spanish Americans in South Colorado.2 The prevalence of NPC in the general population has been estimated at between one in 100,000 and one in 150,000 live births,3โ€“6 although the incidence in the genetically isolated populations is higher.2,7 Of these cases, approximately 20% experience symptomatic onset during adolescence and adulthood,8 resulting in an estimated adult prevalence of one in 500,000 to one in 750,000. Although adult onset is technically defined as symptoms presenting at 18 years of age or over, it may be more relevant to separate both adolescent- and adultonset from childhood-onset NPC. In the adolescent-onset group, the first obvious neurological or psychiatric symptoms appear at 13โ€“14 years of age, and this group of patients is generally phenotypically different from the early-onset (infantile or juvenile) patient group.8โ€“10

While there is no exact figure for the mean age at onset of adult NPC, most patients develop initial signs during the second or third decade,11 although presentation in the sixth decade has been reported.9 Like childhood and adolescent NPC, adult NPC is a progressive disorder and patients usually succumb to illness in their late 30s or 40s.11 The atypical presentation of NPC in adults often leads to its misdiagnosis as other movement disorders or major psychiatric illness.9,11,12 Given the progressive nature of NPC, the high likelihood of misdiagnosis and the presence of available treatment, it is important to increase awareness of this disease among clinicians and provide better knowledge of its manifestation and management.

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